Please use this identifier to cite or link to this item: http://ir.swu.ac.th/jspui/handle/123456789/14598
Title: Pharmacokinetics of deferiprone in patients with β-thalassaemia: Impact of splenectomy and iron status
Authors: Limenta L.M.G.
Jirasomprasert T.
Jittangprasert P.
Wilairat P.
Yamanont P.
Chantharaksri U.
Fucharoen S.
Morales N.P.
Keywords: deferiprone
deferiprone glucuronide
drug metabolite
ferritin
gpo l1
hemoglobin E
iron
iron chelate
transferrin
unclassified drug
adult
area under the curve
article
beta thalassemia
blood sampling
diet restriction
drug activity
drug blood level
drug conjugation
drug efficacy
drug urine level
female
glucuronidation
high performance liquid chromatography
human
iron binding capacity
iron blood level
iron chelation
iron metabolism
iron overload
maximum plasma concentration
multiple linear regression analysis
plasma concentration-time curve
priority journal
single drug dose
splenectomy
urinary excretion
urine volume
Administration, Oral
Adult
Area Under Curve
beta-Thalassemia
Blood Transfusion
Female
Ferritins
Hemoglobin E
Humans
Iron
Iron Chelating Agents
Iron Overload
Male
Pyridones
Splenectomy
Transferrin
Issue Date: 2011
Abstract: Background and Objective: Iron-rich transfusions and/or a compensatory increase in iron absorption ultimately result in iron loading in patients with b-thalassaemia. Hence, without iron chelation, iron accumulates relentlessly. Deferiprone has been shown to be capable of reducing the iron burden in patients with b-thalassaemia. However, there is wide interpatient variation in deferiprone-induced urinary iron excretion (UIE). We hypothesized that splenectomy and iron status might influence the pharmacokinetic profiles of deferiprone in patients with b-thalassaemia/haemoglobin E, and the present study was aimed at examining this hypothesis. Study Participants and Methods: Thirty-one patients with b-thalassaemia/haemoglobin E (20 splenectomized and 11 non-splenectomized patients) were enrolled in the study. After an overnight fast, the subjects received a single oral dose of deferiprone 25mg/kg of bodyweight. Blood samples were collected pre-dosing and at 15, 30, 45, 60, 90, 120, 180, 240, 300, 360 and 480 minutes after dosing. Urine output was pooled and collected at 0-2, 2-4, 4-8, 8-12 and 12-24 hour intervals. Serum and urine concentrations of deferiprone and its metabolite deferiprone glucuronide were determined using a validated high-performance liquid chromatography method. Serum deferiprone-chelated iron and UIE were determined using a validated colourimetric method. Results: No significant difference in the pharmacokinetic parameters of non-conjugated deferiprone was observed between splenectomized and non-splenectomized patients. However, the maximum serum concentration (C max) and the area under the serum concentration-time curve (AUC) from time zero to infinity (AUC 1 ) values of deferiprone glucuronide were significantly lower (both p < 0.05) in splenectomized patients (median 53.2 μmol/L and 12 634 μmol • min/L, respectively) than in non-splenectomized patients (median 70.5 μmol/L and 20 601 mmol • min/L, respectively). The Cmax and the AUCfrom time zero to the time of the last measurable concentration (AUClast) values of serum deferiprone-chelated iron, as well as UIE, were significantly higher (p < 0.001) in splenectomized patients (median values 7.1 μmol/L, 1645 μmol • min/L and 77.1 μmol, respectively) than in non-splenectomized patients (median values 3.1 μmol/L, 545 μmol • min/L and 12.5 μmol, respectively). Urinary excretion of non-conjugated deferiprone and deferiprone glucuronide did not differ between the two groups. Further analyses using multiple linear regressions indicated that the iron profiles (non-transferrin-bound iron and ferritin) were significant predictors of the pharmacokinetic parameters of non-conjugated deferiprone, deferiprone-chelated iron and UIE. In addition, splenectomy status was identified as the strongest predictor of the AUClast of deferiprone-chelated iron and UIE. Conclusion: Both iron and splenectomy status have significant effects on the pharmacokinetics and iron chelation efficacy of deferiprone. A greater degree of iron overload in splenectomized patients results in alterations in pharmacokinetic parameters (theCmax and AUC) of deferiprone glucuronide and deferipronechelated iron, as well as a significant increase in UIE. © 2011 Adis Data Information BV. All rights reserved.
URI: https://www.scopus.com/inward/record.uri?eid=2-s2.0-78649929842&doi=10.2165%2f11536630-000000000-00000&partnerID=40&md5=aa97fef21fc9b8a3faf03a1d169c3fea
http://ir.swu.ac.th/jspui/handle/123456789/14598
ISSN: 3125963
Appears in Collections:Scopus 1983-2021

Files in This Item:
There are no files associated with this item.


Items in SWU repository are protected by copyright, with all rights reserved, unless otherwise indicated.